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. 2019 Jun 15;125(12):2002-2010.
doi: 10.1002/cncr.31994. Epub 2019 Mar 11.

Clinical and molecular characterization of early-onset colorectal cancer

Alexandra N Willauer  1 , Yusha Liu  2 , Allan A L Pereira  1 , Michael Lam  1 , Jeffrey S Morris  3 , Kanwal P S Raghav  1 , Van K Morris  1 , David Menter  1 , Russell Broaddus  4 , Funda Meric-Bernstam  5 , Andrea Hayes-Jordan  6 , Winston Huh  7 , Michael J Overman  1 , Scott Kopetz  1 , Jonathan M Loree  1
Affiliations

Clinical and molecular characterization of early-onset colorectal cancer

Alexandra N Willauer et al. Cancer. .

Abstract

Background: Colorectal cancer (CRC) incidence is increasing in adults younger than 50 years. This study evaluated clinical and molecular features to identify those features unique to early-onset CRC that differentiate these patients from patients 50 years old or older.

Methods: Baseline characteristics were evaluated according to the CRC onset age with 3 independent cohorts. A fourth cohort was used to describe the impact of age on the consensus molecular subtype (CMS) prevalence.

Results: This retrospective review of more than 36,000 patients with CRC showed that early-onset patients were more likely to have microsatellite instability (P = .038), synchronous metastatic disease (P = .009), primary tumors in the distal colon or rectum (P < .0001), and fewer BRAF V600 mutations (P < .001) in comparison with patients 50 years old or older. Patients aged 18 to 29 years had fewer adenomatous polyposis coli (APC) mutations (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.35-0.90; P = .015) and an increased prevalence of signet ring histology (OR, 4.89; 95% CI, 3.23-7.39; P < .0001) in comparison with other patients younger than 50 years. In patients younger than 40 years, CMS1 was the most common subtype, whereas CMS3 and CMS4 were uncommon (P = .003). CMS2 was relatively stable across age groups. Early-onset patients with inflammatory bowel disease were more likely to have mucinous or signet ring histology (OR, 5.54; 95% CI, 2.24-13.74; P = .0004) and less likely to have APC mutations (OR, 0.24; 95% CI, 0.07-0.75; P = .019) in comparison with early-onset patients without predisposing conditions.

Conclusions: Early-onset CRC is not only distinct from traditional CRC: special consideration should be given to and further investigations should be performed for both very young patients with CRC (18-29 years) and those with predisposing conditions. The etiology of the high rate of CMS1 in patients younger than 40 years deserves further exploration.

Keywords: CpG island methylator phenotype (CIMP); age; colorectal cancer; consensus molecular subtypes; early onset; hereditary; inflammatory bowel disease; mutations.

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Figures

Figure 1:
Figure 1:
Cohorts utilized in this study. Sub-caption: MDACC = MD Anderson Cancer Center. AACR = American Association for Cancer Research. GENIE = Genomics Evidence Neoplasia Information Exchange. CMS = Consensus Molecular Subtypes. TCGA = The Cancer Genome Atlas. CRC = colorectal cancer.
Figure 2:
Figure 2:
Mutation prevalence in metastatic colorectal cancer patients according to age at diagnosis in MDACC molecular cohort. Sub-caption: CI = confidence interval. Total number (N) = 1,877.
Figure 3:
Figure 3:
Prevalence of Consensus Molecular Subtypes (CMS) by age. Sub-caption: CI = confidence interval. Total number (N) = 626; N for CMS1=110, CMS2=287, CMS3=79, CMS4=149.
See this image and copyright information in PMC

Comment in

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